The phrenic and intercostal motoneuron pools provide the major innervation for the respiratory muscles. Most studies have concentrated on brainstem sites of respiratory control. The medullary and pontine nuclei which control the phrenic and intercostal motoneurons have been identified, their bulbospinal pathways have been mapped, and the temporal characteristics of the projection pathways are known. Much less is known about the transmitter mechanisms involved in respiratory control. In the spinal cord, our knowledge of respiratory transmitter mechanisms is practically nonexistant, despite the fact that considerable neural processing and integration takes place at this level. This project will determine if several potential inhibitory neurotransmitter candidates are, operative at spinal synapses which control intercostal and phrenic motoneurons. Electrophysiological and neuropharmacological experiments will be performed on anesthetized and unanesthetized decerebrate cats. Electrophysiological methods will include peripheral nerve recording from phrenic and intercostal nerves, and recording from phrenic and intercostal motoneurons with micropipettes. In neuropharmacological studies, putative neurotransmitters and their antagonists will be administered directly to single neurons by microelectrophoresis. Neurotransmitter candidates to be evaluated are serotonin, norepinephrine, Gamma-aminobutyric acid andglycine. This study will determine: (1) If these candidates are effective in modifying transmission at spinal respiratory synapses; (2) If any of the transmitter candidates inhibit motoneurons during the "off-phase" of the respiratory cycle (3) If any of the candidates appear to be involved in the inhibitory Hering-Breuer reflex. Answers to the questions asked in this project will have important long-term consequences. First, information will be obtained which may have application to the synaptic physiology of other less accessible, and more complex supraspinal respiratory circuits. Second, the data will provide a framework for neuropharmcological studies of drugs which have therapeutic or adverse effects on respiration.